Homeostatic Expansion of CD4+ T Cells Promotes Cortical and Trabecular Bone Loss, Whereas CD8+ T Cells Induce Trabecular Bone Loss Only
| Autor: | Tatyana Vikulina, Susanne Roser-Page, M. Neale Weitzmann, Masayoshi Yamaguchi, Ighovwerha Ofotokun |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult CD4-Positive T-Lymphocytes Male medicine.medical_specialty Adoptive cell transfer Anti-HIV Agents Osteoporosis Inflammation HIV Infections CD8-Positive T-Lymphocytes Bone remodeling 03 medical and health sciences Major Articles and Brief Reports 0302 clinical medicine Bone Density Internal medicine medicine Immunology and Allergy Cytotoxic T cell Humans 030212 general & internal medicine Bone Resorption Bone mineral Chemistry Middle Aged medicine.disease 030104 developmental biology Infectious Diseases medicine.anatomical_structure Endocrinology Cortical bone Female medicine.symptom CD8 |
| Zdroj: | The Journal of infectious diseases. 216(9) |
| ISSN: | 1537-6613 |
| Popis: | Background Bone loss occurs in human immunodeficiency virus (HIV) infection but paradoxically is intensified by HIV-associated antiretroviral therapy (ART), resulting in an increased fracture incidence that is largely independent of ART regimen. Inflammation in the bone microenvironment associated with T-cell repopulation following ART initiation may explain ART-induced bone loss. Indeed, we have reported that reconstitution of CD3+ T cells in immunodeficient mice mimics ART-induced bone loss observed in humans. In this study, we quantified the relative effects of CD4+ and CD8+ T-cell subsets on bone. Methods T-cell subsets in T-cell receptor β knockout mice were reconstituted by adoptive transfer with CD4+ or CD8+ T-cells subsets were reconstituted in T-cell receptor β knockout mice by adoptive transfer, and bone turnover, bone mineral density, and indices of bone structure and turnover were quantified. Results Repopulating CD4+ but not CD8+ T cells significantly diminished bone mineral density. However, micro-computed tomography revealed robust deterioration of trabecular bone volume by both subsets, while CD4+ T cells additionally induced cortical bone loss. Conclusions CD4+ T-cell reconstitution, a key function of ART, causes significant cortical and trabecular bone loss. CD8+ T cells may further contribute to trabecular bone loss in some patients with advanced AIDS, in whom CD8+ T cells may also be depleted. Our data suggest that bone densitometry used for assessment of the condition of bone in humans may significantly underestimate trabecular bone damage sustained by ART. |
| Databáze: | OpenAIRE |
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